It is oftentimes desirable in biomedical applications to analyze multiple physical properties and/or constituents of small volume samples of a patient's bodily fluid. For example, samples of a patient's whole blood are oftentimes analyzed and/or monitored so as to provide information regarding blood analytes such as pH, PCO.sub.2, PO.sub.2, K.sup.+, Na.sup.+, Ca.sup.2+, Cl.sup.-, and the like. Information derived from blood analytes in a sample is compared to normal physiological functions and homeostasis profiles and thereby used by the attending physician for diagnostic purposes and/or to control life support systems.
Systems which employ electrochemical electrodes for detecting constituents of a bodily fluid, for example whole blood, are in and of themselves well known as evidenced from U.S. Pat. Nos. 3,658,478 to Spergel et al, 5,387,329 to Foos et al, 5,338,435 to Betts et al, 4,734,184 to Burleigh et al, 4,361,539 to Weinberg et al and 5,200,051 to Cozzette et al (the entire content of each patent being expressly incorporated hereinto by reference). While the sensor systems disclosed in the prior art may reasonably be satisfactory for their intended purposes, further improvements to decrease cost and to increase manufacturing yield, reliability, shelf life, operating life and user convenience are still desired. In order to realize all these further improvements simultaneously, there have been a number of recent efforts and subsequent patents to miniaturize the sensors themselves and to fabricate them by techniques recently made available by developments in integrated circuit technology. In this regard, integrated circuit technology allows sensors to be fabricated in a planar format whereby thin layers of materials are applied successively to a base dielectric substrate using thick-film and/or thin-film techniques. The manufacture of planar sensors can be significantly automated to allow production in quantity and at lower cost. Planar sensors can be made smaller and configured more closely together, reducing the sample volume requirements.
Historically, the design of microsensors has largely involved simply the miniaturization of macrosensor technology. Performance expectations, however, have not been realized--in large measure because of the poor chemical stability of small sensor assemblies as evidenced both by short operating life and by unacceptable drift rates over that life. Additional constraints are placed on the design of microsensor that are to be manufactured in compact arrays. To the performance criteria currently applied in the evaluation of conventional sensing electrodes must be added an important further constraint--namely, in order to exploit these developments in integrated circuit technology and realize the economies of bulk manufacture in compact arrays, it is necessary that all sensor types have generally the same design and structure involving more or less the same fabrication techniques.
For example, most prior art systems include a sensor array which itself defines one wall of the flow channel. Thus, in order to limit sample volume requirements, the channel cross-section and/or length must be reduced which, in turn, limit the sensor membrane cross-section and its total volume. The adverse consequence of limiting membrane cross-section and/or volume under these circumstances is that the useful life of the sensor is reduced.
On the other hand, if, in order to increase the membrane diameter, the width of the channel is increased locally without increasing the cross-section of the channel throughout, then one or more fluid pockets will be formed in the flow channel which tends to aggravate any clean-out problems and increases the sample volume needed to assure a clean, uncontaminated sample segment in front of the sensors during the actual time of measurement. Local increases in the cross-section of the channel also disadvantageously promote sample degassing.
The limits to the cross-sectional area of the membrane also limits the bonding area between the membrane and its support substrate and any possible sealing area between the membrane and the flow channel. The limited bonding area between the membrane and the substrate requires very tight tolerances for membrane deposition and a relatively frequent incidence of loss of adhesion. Sensor failures can thus ensue as a direct consequence of such limited bonding areas.
In many prior art sensor systems, the entire surface area of the membrane is exposed to the sample stream. For example, as disclosed in the above-cited Betts et al '435 and Burleigh et al '184 patents, the membrane is thereby entirely exposed to the sample in the flow path. However, the fact that the entire surface area of the membrane is exposed to the sample stream leaves no opportunity for mechanical capture of the membrane between the substrate layer supporting the membrane and the layer defining the flow channel of the sensor module. Furthermore, in those prior art systems where the entire membrane area is exposed to the sample stream, bonding between the membrane and the substrate is achieved solely by direct adhesion, and so membranes that do not chemically bond to the substrate surface may delaminate, thereby again causing sensor failures.
The problems discussed above become particularly acute when multiple sensor arrays are provided in clusters so as to be capable of detecting a corresponding multitude of physical properties and/or constituents in a single fluid sample.
What has been needed in this art, therefore, is a sensor cartridge having plural (i.e., at least two, or more) fluid constituent-selective membranes which are self-aligning and self-sealing with respect to a fluid sensing port associated with the sensor cartridge's fluid flow path. It is toward fulfilling such a need that the present invention is directed.
Broadly, the present invention is embodied in a sensor cartridge in which a fluid constituent-selective sensor membrane is in direct sealing contact with a face of a flow-through sample cell entirely around a sensor port of the flow channel. In other words, the sensor membrane has sufficiently large surface area so as to entirely cover the sensor port and also establish an annular region in surrounding relationship to the sensor port. It is this annular region which is in direct contact with a corresponding region of the sample cell face so as to provide self-sealing capabilities. Moreover, the sensor membrane is self-aligning with the sensor port since it has a sufficiently large area to ensure complete coverage of the sensor port. Thus, according to the present invention the diameter of the sensor membrane is no longer dependent on the cross-sectional dimension of the flow channel supplying sample fluid to the sensor port.
In a particularly preferred embodiment of this invention, the sensor cartridge includes a flow-through sample cell having a zig-zag flow channel so as to provide a series of sensor ports on both of the opposed cell faces. A pair of sensor arrays having a corresponding series of individual sensors are thus juxtaposed with a respective sample cell face so as to sandwich the sample cell therebetween. The individual sensors are provided with sensor membranes selective to a desired fluid constituent to be determined and are connected electrically to peripheral detection hardware. Each of the individual sensors thus electrochemically determines a particular fluid constituent which is communicated electrically to the peripheral hardware where it may be displayed in human-readable form.
Furthermore, according to the present invention, the ratio of the membrane surface area exposed to the sample stream compared to the total membrane surface area is such that most of the membrane surface is not subject to extraction into the sample stream. Thus, the bulk of the membrane functions as a reservoir of critical components against the early depletion of the membrane.
The sandwiched sample cell and sensor arrays are most preferably contained within a two-part "clamshell" housing. The term "clamshell" as used herein and in the accompanying claims is meant to refer to a two part, bilaterally symmetrical outer shell that encases the flow chamber on at least two of its sides. The housing may or may not include hinge structures so as to allow the two parts thereof to be hingedly moved relative to one another and thereby gain access to the flow chamber. The housing includes biasing members (most preferably in the form of a resilient elastomeric pad) which serve to bias the sensor membranes into direct sealing contact with their respective sample cell faces around the sensor port.
The arrangement of the present invention therefore offers an important advantage in terms of the angle of approach of the sample path to the sensor membranes in that the sample stream contacts the membrane only at its center. As a result, single, discrete sensors on separate individual chips may be aligned contiguously without unacceptably increasing the potential for leaks in the fluid path. This, in turn, leads to significant manufacturing and test advantages.
Further aspects and advantages of this invention will become more clear after careful consideration is given to the following detailed description of the preferred exemplary embodiment thereof.